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Despite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose.ENSEMBLE2 is a randomised, double-blind, placebo-controlled, phase 3 trial including crossover vaccination after emergency authorisation of COVID-19 vaccines. Adults aged at least 18 years without previous COVID-19 vaccination at public and private medical practices and hospitals in Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA were randomly assigned 1:1 via a computer algorithm to receive intramuscularly administered Ad26.COV2.S as a primary dose plus a booster dose at 2 months or two placebo injections 2 months apart. The primary endpoint was vaccine efficacy against the first occurrence of molecularly confirmed moderate to severe-critical COVID-19 with onset at least 14 days after booster vaccination, which was assessed in participants who received two doses of vaccine or placebo, were negative for SARS-CoV-2 by PCR at baseline and on serology at baseline and day 71, had no major protocol deviations, and were at risk of COVID-19 (ie, had no PCR-positive result or discontinued the study before day 71). Safety was assessed in all participants; reactogenicity, in terms of solicited local and systemic adverse events, was assessed as a secondary endpoint in a safety subset (approximately 6000 randomly selected participants). The trial is registered with ClinicalTrials.gov, NCT04614948, and is ongoing.Enrolment began on Nov 16, 2020, and the primary analysis data cutoff was June 25, 2021. From 34 571 participants screened, the double-blind phase enrolled 31 300 participants, 14 492 of whom received two doses (7484 in the Ad26.COV2.S group and 7008 in the placebo group) and 11 639 of whom were eligible for inclusion in the assessment of the primary endpoint (6024 in the Ad26.COV2.S group and 5615 in the placebo group). The median (IQR) follow-up post-booster vaccination was 36·0 (15·0-62·0) days. Vaccine efficacy was 75·2% (adjusted 95% CI 54·6-87·3) against moderate to severe-critical COVID-19 (14 cases in the Ad26.COV2.S group and 52 cases in the placebo group). Most cases were due to the variants alpha (B.1.1.7) and mu (B.1.621); endpoints for the primary analysis accrued from Nov 16, 2020, to June 25, 2021, before the global dominance of delta (B.1.617.2) or omicron (B.1.1.529). The booster vaccine exhibited an acceptable safety profile. The overall frequencies of solicited local and systemic adverse events (evaluated in the safety subset, n=6067) were higher among vaccine recipients than placebo recipients after the primary and booster doses. The frequency of solicited adverse events in the Ad26.COV2.S group were similar following the primary and booster vaccinations (local adverse events, 1676 [55·6%] of 3015 vs 896 [57·5%] of 1559, respectively; systemic adverse events, 1764 [58·5%] of 3015 vs 821 [52·7%] of 1559, respectively). Solicited adverse events were transient and mostly grade 1-2 in severity.A homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19. Studies assessing efficacy against newer variants and with longer follow-up are needed.Janssen ResearchDevelopment.

The coastal zones of Small Island States are hotspots of human habitation and economic endeavour. In the Pacific region, as elsewhere, there are large gaps in understandings of the exposure and vulnerability of people in coastal zones. The 22 Pacific Countries and Territories (PICTs) are poorly represented in global analyses of vulnerability to seaward risks. We combine several data sources to estimate populations to zones 1, 5 and 10 km from the coastline in each of the PICTs. Regional patterns in the proximity of Pacific people to the coast are dominated by Papua New Guinea. Overall, ca. half the population of the Pacific resides within 10 km of the coast but this jumps to 97% when Papua New Guinea is excluded. A quarter of Pacific people live within 1 km of the coast, but without PNG this increases to slightly more than half. Excluding PNG, 90% of Pacific Islanders live within 5 km of the coast. All of the population in the coral atoll nations of Tokelau and Tuvalu live within a km of the ocean. Results using two global datasets, the SEDAC-CIESIN Gridded Population of the World v4 (GPWv4) and the Oak Ridge National Laboratory Landscan differed: Landscan under-dispersed population, overestimating numbers in urban centres and underestimating population in rural areas and GPWv4 over-dispersed the population. In addition to errors introduced by the allocation models of the two methods, errors were introduced as artefacts of allocating households to 1 km x 1 km grid cell data (30 arc-seconds) to polygons. The limited utility of LandScan and GPWv4 in advancing this analysis may be overcome with more spatially resolved census data and the inclusion of elevation above sea level as an important dimension of vulnerability.